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Leishmania major Amastigotes Induce p50/c-Rel NF-B Transcription Factor in Human Macrophages: Involvement in Cytokine Synthesis

Lamia Guizani-Tabbane,^* Khadija Ben-Aissa, Meriam Belghith, Atfa Sassi, and Koussay Dellagi

Laboratory of Immunology, Vaccinology and Molecular Genetics (WHO Collaborating Center for Research and Training in Leishmaniasis), Institut Pasteur de Tunis, 1002 Tunis-Belvedere, Tunisia

Received 17 September 2003/ Returned for modification 27 November 2003/ Accepted 28 January 2004

Invasion of a host by pathogens is frequently associated with activation of nuclear factor kappa B (NF-B), which is implicated in various aspects of immune function required for resistance to infection. However, pathogens may also subdue these mechanisms to secure their survival. Here we describe the effect of Leishmania major infection on NF-B transcription factor activation in both promonocytic human cell line U937 and fresh human monocytes. Infection by L. major amastigotes blocked nuclear translocation of a phorbol-12 myristate-13 acetate (PMA)-induced p50/p65 NF-B complex in PMA-treated differentiated U937 cells and triggered expression of p50- and c-Rel-containing complexes in both U937 cells and fresh human monocytes. These p50/c-Rel complexes, triggered by direct cell-parasite interactions, were detectable within 30 min after the interaction and were transcriptionally active. The NF-B inhibitor caffeic acid phenethyl ester inhibited production of both tumor necrosis factor alpha and interleukin-10 (IL-10) induced by Leishmania amastigotes in differentiated U937 cells. Similar results for IL-10 induction were observed with amastigote-infected human monocytes. Our results indicate that L. major amastigotes activate NF-B by specifically inducing p50- and c-Rel-containing complexes which are likely involved in the regulation of cytokine synthesis.

Editor: B. B. Finlay

L.G.-T. and K.B.-A. contributed equally to this work.

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